
So welcome back. 
So, today we want to talk about the 
endocrine system, and they and we only 
want to talk about it in general concepts 
or general terms. 
And then we actually go through the 
endocrine system a little later in the 
course. 
We're going to look at very specific, 
endocrine glands. 
But today we're going to look over the 
entire sort of an overview of the entire 
system. 
So, the first things we want to talk 
about is to concen, to contrast the 
endocrine reflex loop with local control. 
And then secondly, we want to 
characterize hormonal classes. 
And this, going to be classified by 
according to their chemical nature. 
Third, we want to explain the role of the 
carrier proteins in the cases where we 
have a hydrophobic molecule and has to be 
immediately delivered through the blood 
through an endocrine system to the 
tissues. 
Four, we want to explain the differences 
between the receptors types and the 
different classes of these hormones and 
then we want to explain the differences 
in their stimuli. 
And then lastly explain differences in 
regulation. 
Okay, so there's quite a bit of things to 
go over. 
So, let's start. 
So, the first thing is that this is one 
of the major homeostatic control systems 
of the body. 
The other one of course is the nervous 
system. 
But you have also local control systems. 
And the local control systems are 
occurring at the target cells themselves. 
So, the target cells are the cells that 
have [INAUDIBLE] receptors. 
That is approaching, that can recognize 
the specific chemical. 
And we've said in the homeostatic le, eh, 
homeostasis lectures that the, we've have 
a, a situation where a chemical can be 
secreted from the first cell and it works 
on its neighboring cell and that chemical 
is called a paracrine. 
But we can also have the cell secreting a 
chemical that works on itself. 
And that that's then called an autocrine. 
These are not considered to be hormones. 
They're see, secreted into the 
interstitial space and they work locally. 
The homeostatic controls that we are 
talking about when we're talking about 
the endocrine system is that we have a 
cell that's going to secrete its chemical 
into the blood. 
And then the blood is going to, to 
deliver it to the target cells. 
Those are the cells that have receptors 
for the hormone or for that chemical. 
All of the cells of the body will be 
bathed by these hormones. 
They're all going to see the hormone. 
But unless they have a receptor for the 
hormone, they can't recognize the hormone 
and will not respond to the hormone. 
The, the second thing that we have to 
remember about this system is that it's 
secrecting, it, these chemicals are being 
secreted into the blood, and the blood is 
effectively three and a half liters of, 
of plasma. 
So, you have three and a half liters of 
fluid and they, the chemical then is 
going to be diluted into this very large 
volume. 
Because of that, the chemical will be in 
very, very, very low concentrations. 
And because they're at low 
concentrations, picomolar or nanomolar 
range concentrations, they have to have 
very, very high affinity receptors 
sitting on their cell services. 
So, the target cell has a high affinity 
receptor. 
And the chemical, the hormone in the 
blood, the concentration of the hormone 
is going to be very low or very dilute. 
So, we have very low concentration of 
very dilute signals. 
This is in contrast to the nervous 
system, which is our other, major 
communication system of the body. 
And here, the nerve is going to secrete 
it's chemical into a very tiny space, 
which is called the synapse, and that's 
almost budding up against its target 
cell. 
So, it's a very very small space and so 
the amount of neurotransmitter being 
released will be in very high 
concentration at the target cells, 
receptors. 
So, the target cell receptors then, will 
have low affinity. 
They have low affinity. 
That means that the binding of the hor, 
of the neurotransmitter to that receptor 
is very rapid, but it'll come off very 
quickly from that receptor. 
So, we have, in the nervous system then, 
we have a high concentration of the 
neurotransmitter. 
And the target cell, the receptor on the 
target cell, it's going to have a low 
affinity receptor. 
The other thing we need to remember about 
the endocrine system is that these are 
ductless glands so that the secretions 
from these hormones is going to go 
straight into the capillary beds that are 
perfusing all of these cells. 
There are no ducts that are taking the 
material then, from the gland and 
depositing it at, at a distance. 
The second thing is that the endocrine 
glands are going to regulate many of the 
homeostatic missions of the body. 
So, they're going to regulate the sodium 
and water balance, the calcium balance, 
energy balance, processes that cope with 
stress, growth and development and 
processes that are associated with 
reproduction. 
And as we go through the course we're 
going to talk about each of the endocrine 
systems that are in fact mediating each 
of these different homeostatic functions. 
The other thing about endocrine system is 
that the concentration of the hormone is 
critical. 
If we have too high of a concentration 
then we have too much of a stimulus. 
We have too great of a stimulus. 
We can down regulate the receptors so 
that the receptors then are on the target 
cells are not available. 
So that, on the other hand if we have too 
low of a concentration, not enough of the 
receptors are activated on the target 
cells and we don't get a big enough 
biological response. 
So, the hormones, the concentration of 
the hormone in the blood, is, you want to 
have it at what's called u, a u 
concentration. 
And this is where it is not it is at the 
normal concentration where we will get an 
adequate response from the receptor. 
The rate of the production of the hormone 
is going to be our most regulated aspect, 
and it is going to be regulated by both 
positive and negative feedback loops. 
The other thing about the hormone system 
is that the hormones are delivered by the 
blood. 
And because they are delivered by the 
blood it's a very, very slow delivery. 
With the nervous system, the nerve is 
budding right up against its target cell 
so the, the response is immediate. 
It's within seconds. 
But with the, with the hormonal system 
the response can be minutes to hours. 
So, it's much, much slower type of 
response. 
The other thing about it is that the 
delivery of these hormones can be 
dependent on mass action, because some of 
these hormones are bound to carriers. 
So, if the hormone is bound to its 
carrier, which is what was shown here, 
then that hormone can come off from the 
carrier and become a free agent. 
So, it's free within the bloodstream, and 
then it can be, is able to bind to its 
receptor. 
Which is going to be on the cell or 
within the cell. 
In the case of the hormones that are 
bound to carriers, these are usually 
steroid hormones. 
These are usually lipid soluble hormones, 
so they have to be bound to a carrier in 
order to be able to move through the 
bloodstream. 
So, they're bound to a protein carrier 
and this protein carrier then, has to 
have low affinity so that the hormone can 
be pulled off the carrier to bind to the 
target cell receptor. 
Because we want the hormone to be 
released from the carrier to bind to its 
receptor, which has high affinity. 
So the, the re, ex, equation then is 
pulled towards the receptor and this is 
what's known by mass action laws. 
And then lastly, the hormone will be 
governed, the concentration of the 
hormone will be governed by its rate of 
degradation, or removal from the body. 
And it can be degraded either in the 
liver or by the kidney, excreted by the 
kidney. 
Okay, so we have actually three different 
types of hormones and we can classify 
them by their chemical nature. 
The first are the peptide or protein 
hormones. 
These can be anywhere from three amino 
acids or bigger. 
These hormones are first synthesized on 
rough endoplasmic reticulum as what is 
known as the preprohormone. 
This is an inactive species. 
And the preprohormone then this protein 
will be further cleaved as it's packaged 
and moved to the golgi. 
And once it's in the golgi, which is 
another, another organelle system within 
the body, then it's cleave to a 
prohormone. 
In some cases, the prohormone is active 
but in most cases the prohormone is also 
inactive. 
And in the golgi, then this, these 
hormones will be packaged into secretory 
vesicles and the secretory vesicles. 
Then with the stored hormone inside the 
hormone is now cleaved one more time to 
form the active species. 
So, the prohormone then is cleaved to 
give us the active hormone and that's 
occurring within secretory vessels. 
And these cells that are secreting this 
the peptide or protein hormones the 
secretory vessels packaged with the 
hormone, these secretory vessels can sit 
inside of plasma for long periods of 
time. 
And they'll sit there until there's a 
secretagogue that is a signal that comes 
to the cell. 
It tells a cell to secrete it. 
The, the cell then will have an increase 
in calcium in the inter cellular calcium 
or an increase in cyclic ANP. 
And either of those signals will cause 
then the, the secretion of these hormones 
from, from the cell. 
But these hormones are prepackaged and 
because they're prepackaged they can be 
released as needed. 
So, they're synthesized and they're 
waiting for the signal to be secreted. 
The other thing about these is that they 
are proteins so once they are into the 
blood they have a very short half life. 
So, we have short half lives. 
They do not require a carrier because 
they are soluble within, within the 
plasma. 
And they are synthesized and stored. 
[SOUND] An example of one of these 
hormones would be insulin. 
So, insulin, for instance, is made as a 
preprohormone. 
Insulin is packaged is, is then cleaved 
as it moves from the rough endoplasma 
reticulum to, to the golgi and there it's 
packaged into vessicles. 
And then once it moves into the vescicle, 
the insulin then becomes cleaved. 
The cleavage section from the insulin 
molecule is called the c-peptide. 
And it turns out that the c-peptide also 
have biological activity. 
And the two are going to be present in 
equal molar ratio within, within the 
vesicle. 
When the insulin is secreted, this 
peptide is also released into the blood. 
The second type of hormone are the 
hormones that are derivative, derivatives 
of cholesterol. 
And these hormones are called steroid 
hormones. 
They are made by the adrenal glands. 
By the gonads and by the placenta of a 
pregnant female. 
These steroid hormones are not soluble in 
plasma. 
They are liquid soluble so they have to 
be transported in the blood on carrier 
proteins. 
These hormones have to be synthesized on 
demand, they can not be stored within 
membrane bound vesicles within the 
cytoplasm. 
Because they are able to go across the 
plasma, the little membrane vesicles they 
are soluble and lipid. 
So, when you need any of these hormones 
then they have to be synthesized. 
Once they are synthesized then they have 
to be secreted. 
So, these hormones take a little bit more 
time for them to act, to increase in 
tighter or increase in the amount within, 
within the blood. 
The other thing is they have to be 
transported on carrier proteins, so they 
are bound to the carrier protein. 
The carrier protein is made in the liver, 
they're bound to the carrier protein and 
then delivered to the tissues. 
Then pulled off from the carrier protein, 
and then used within the tissues. 
Many times, these steroid hormones are 
converted to more active species within 
the target tissues and we'll talk about 
that when we get to the, to the specific 
instances. 
For the instance on the testosterone, 
which is made in the male. 
This is the male sex hormone. 
The testosterone can be converted to a 
much more, higher active form, which is 
dihydrotestosterone, which is a DHT. 
Testosterone can also be converted from 
the male hormone, can be converted to 
estrogen, within the tissue as well. 
So, testosterone can be converted by an 
enzyme either to DHT or estrogyn 
depending on upon the target tissue. 
The last of these hormones is the amino 
acid derivatives, and what's shown here 
are derivatives of tyrosine. 
So, we have epinephrine is one of these 
hormones. 
It's made in the adrenal gland. 
The epinephrine is soluble in plasma and 
has a very short half life of seconds to 
minutes. 
The epinephrine will bind to the same 
receptors that, adrenergic receptors, 
that the neuro neuroepinephrine binds to. 
So, it's it's sort of a back up system 
for the sympathetic nervous system. 
Tyrosine derivatives are, can also be 
made into thyroxine or into T3. 
So, thyroxine, which is shown here, is 
the thyroid hormone. 
These are insoluble in plasma. 
They are transported via carriers to 
their target tissues and they have a very 
long half life because they are bound to 
the carrier their half lives are on the 
order of hours to days. 
And in fact, these hormones have a half 
life, t4 has a half life of seven days. 
Interestingly enough these hormones are 
converted in the target tissues, so t4, 
which is what' shown here. 
Because it has four iodine residues on it 
can be converted to t3, which is the 
other active species by removing one of 
the, by removing one of the iodines. 
So, let's talk a little bit about the 
transport carriers. 
The transport carriers as I said extend 
the life of the hormone in the blood, and 
the thyroid hormones it's several days, 
the steroid hormones, testosterone and 
estrogen is on the order of 60 to 90 
minutes. 
They also importantly they sequester the 
hormone from its target cell. 
As long as the hormone is on the carrier 
and is bound to the carrier it's not able 
to enter into, to engage to the receptor. 
So, the only hormone that's actually 
active of these is going to be the free 
hormone and the free hormone is going to 
be in very, very small concentrations 
within the blood. 
Because it's not very soluble within the 
blood. 
So, it's being released from the carrier, 
just locally at the tissue, and, and 
that's that will be the carrier, that 
will be the hormone that's able to bind 
to its receptor. 
The total concentration of the hormone is 
going to reflect the free plus the bound. 
So, as you look at the total 
concentration then by say, an antibody 
acid, You will see what's bound as well 
as what's free, but it's only the free 
that's going to be active. 
So, why is this important? 
You could have an instance where you have 
an individual who is put on birth control 
pills, so she's taking estrogen. 
and as she's taking estrogen estrogen 
causes a secretion of a hormone, of a 
carrier from the liver for the thyroid 
hormone. 
So her total amounts of thyroid hormone 
which are circulating within the blood 
can rise. 
But most, but this hormone his then bound 
to this new carrier to this extra 
carrier. 
And even though you have a large amount 
of, of material that's bound to the 
carrier, its the free hormone that's the 
important amount. 
So, the person could have normal amounts 
of free hormone but very high amounts of 
hormone bound to a carrier and be 
perfectly normal. 
And w'ell talk about this some more when 
we talk about the thyroid gland. 
Now, these different classes of hormones 
also differ in their receptor types. 
So, the hormones, which are soluble in 
plasma, they're the ones that are, are 
are hydrophilic materials so, the peptide 
derivatives. 
They bind to, receptors, which are 
present on the cell surface and that's 
what's shown here. 
And there are essentially three different 
types of receptors that they can bind to. 
These receptors are integral membrane 
proteins so they're inserted within the 
plasma membrane. 
The first is one where you have a 
tyrosine kinase linked situation, and 
this is the receptor for growth hormone. 
What this means is that the hormone when 
the hormone binds to this receptor that 
a, a enzyme, which is tyrosine kinase. 
It's Kinase means it puts a phosphate 
group on something. 
Is, is recruited to the receptor. 
And then that second messenger signaling 
then starts a cascade of events, which 
changes the metabolism of the cell. 
In the second case, which is the case of 
insulin, the insulin binds to its 
receptor. 
That receptor itself is a tyrosine 
kinase. 
Binding of the insulin to its receptor 
activates the tyrosine kinase and you now 
get a phosphorylation cascade where we 
change again the metabolism of the cell. 
And again, its a very rapid second 
messenger signaling within the cell. 
And the last one are the G-coupled 
receptors, and the G-coupled receptors 
are using, in some cases, adenylate 
cyclase to cause metabolic changes within 
the cells. 
And again, we're activating second 
messenger cascades which will then 
rapidly change the metabolism of the 
cell. 
And this is the type of receptor that we 
see for glucagon. 
We also have these steroid hormones and 
the thyroid hormones and they're both 
soluble in liquid. 
And so, these two hormones, these types 
of hormones can cross the plasma membrane 
and enter directly into the interior of 
the cell. 
Because they can enter into the interior 
of the cell, their receptors are inside 
the cells. 
So, these receptors are receptors that 
are going to bind to the DNA and activate 
gene transcription. 
That is, they're going to change the type 
of messenger RNA and proteins that are 
going to be made by this particular cell. 
They're changing the activity of the DNA. 
They're, the, in every case we can have 
multiple types of receptors on a target 
cell. 
For instance, the beta the cell of the 
pancreas has receptors on it that 
regulate its activity and these 
receptors, there can be receptors for 
epinephrine on it, and there's also 
receptors for [UNKNOWN] on that same 
cell. 
So, it's going to the net effect of these 
receptors and whether they're activated 
and how activated they are will be the, 
determine, how the outcome from that 
given gland or from that given cell. 
The other thing you should remember is 
there are large numbers of these 
receptors on the cell's surface. 
There's not just one receptor on the 
cell's surface but many many copies of 
receptors on the cell's surface. 
And also many copies of the transcription 
factors, that is the nuclear receptors, 
which are within these cells. 
for binding the steroid hormones or for 
binding the thyroid hormones. 
The target cell sensitivity is, depends 
on its receptor, so the affinity of the 
receptors, as we said has to be high 
affinity for these hormones, because we 
have very low concentrations of the 
hormone. 
Secondly the receptor number, cells that 
target cells that have very high numbers 
of receptors on itself surface for a 
given hormone are very, very sensitive to 
that particular hormone. 
So, and then third, competition. 
Competition is that some of these 
hormones are very similar in structure 
and they can bind to the receptors, so 
for instance. 
The mineral cortecode receptor, cortesol 
can bind to it and aldostrin can combine 
to it. 
And to prevent cortesol from binding to 
that mineral cortecode receptor then the 
cell has a protective mechanism for 
inactivating the cortesol. 
And lastly, saturation and again, this is 
when all of the receptors that are 
present on the cell surface are, are 
bound by, by the hormone. 
So, this is, all of the receptors are 
occupied so we have maximum activity at 
that time, maximal response from the 
target cell. 
Okay, so it's sort of difficult to think 
about this. 
This is all abstract and I'm giving you 
lists sort of laundry lists of things to 
remember. 
and eh, they're the type of things where 
it's difficult to think about, because 
we're not talking about a particular 
hormone or a particular activity. 
So, let's go through and look at these 
different kinds of of stimuli that can 
activate the, the hormones or the, the 
endocrine systems. 
And the first of these would be that we 
have a neuron that's going to become 
targeted by a stimulus. 
And so, this neuron then is going to 
secrete a hormone. 
And it's going to, called a 
neuroendocrine. 
The, this neuron can sense the 
concentration of sodium that's within the 
blood. 
And by sensing the concentration of 
sodium, as sodium rises, within the 
blood, this, this particular neuron 
becomes actived and secretes a hormone 
called antidiuretic hormone. 
This hormone works on the kidney and 
causes the kidney to move water from the 
presumptive urine back to into the blood. 
So, it dilutes down the amount of sodium 
that's within the blood. 
So, this is called a neural control. 
And, and, the, the neuron is sitting, is 
secreting from what's called the 
posterior pituitary, a part of the brain. 
In the second kind of a situation, we 
have a hormone, which is regulating a 
hormone, which is regulating a hormone, 
which is regulating a hormone. 
So, under these conditions our stimulus 
could be that we have low plasma glucose. 
If we have low plasma glucose, then the 
hypothalamus, again a portion of your 
brain, can sense that from the blood. 
And it will secrete the first hormone, 
which is growth hormone releasing 
hormone. 
That works on the pituitary cell to, to 
secrete growth hormone. 
And the growth hormone then works on the 
liver, which is it's target cell and the 
liver then or the bone, which is, which 
are it's target cells. 
So, here we have one hormone, which is 
controlling another hormone, which is 
controlling a third. 
So, we have a series of hormones, and 
this a complex negative feedback loop. 
And in the last case, we have the 
stimulus directly activates the final, 
the final gland. 
And that is, if we have low blood calcium 
levels, so we have low blood calcium 
levels, we can activate the parathyroid 
gland. 
And the parathyroid gland secretes the 
parathyroid hormone, and the parathyroid 
hormone works on bone, and this bone then 
will release calcium. 
And the calcium then, is a negative 
feedback loop, which removes our original 
initiating signal. 
So, this can be very complicated. 
the other illustration that I could have 
given for this last one is the pancreas 
and that is where we're secreting 
insulin. 
glucose rises in the blood, insulin is 
secreted from the pancreatic data cell, 
this, this then would be insulin. 
And the insulin works on the target cell 
which is the muscle or fat, to take the 
glucose back up into the body. 
So, we're going to have very, very 
complicated systems. 
and we're going to deal with each of 
these systems separately, at a later time 
in, in the course. 
So, how do we, that's how we turn on the 
system so how do we turn off the system? 
We can turn off the system both locally 
and systemically. 
So, we can turn off this system locally 
at the gland itself and this would be 
through receptor desensitization. 
If we simply remove the, the receptor for 
the hormone in the target cell, from the 
cell surface, for instance. 
If it's an insulin receptor we remove it 
from the cell surface, then the target 
cell, which is skeletal muscle cannot see 
the insulin, does not bind the insulin, 
and won't respond. 
The alternative is that you can degrade 
the actual receptor. 
So, you can move it from the target cell 
surface and degrade it. 
The Type II diabetic is actu, is, a 
situation where we have receptor, 
desensitization. 
So, the Type II diabetes is where that 
individual, does not respond correctly to 
insulin. 
Insulin is present in the system, but the 
receptor is desensitized and so you don't 
get movement of glucose from the blood 
into the skeletal muscle cells correctly. 
To hide it, to move this rise in blood 
glucose due to feeding. 
The other way of controlling this is 
through our negative feedback and that's 
obviously what we were just talking about 
where, where if you have the stimulus and 
that was that we had a high sodium within 
the blood. 
And then we move water back by this 
hormone, anti-diuretic hormone. 
We move water back from the kidney to 
dilute that sodium, then we move the 
initiating signal, and that's simply a 
regular negative feedback system. 
Okay, so what are our general concepts 
then, the first is that we have peptide 
hormones and they're soluble in plasma, 
they bind to cell surface receptors, 
they're fast-acting and they're going to 
have short half-lives. 
Secondly, we have thyroid hormones and 
steroid hormones, and these are insoluble 
in plasma. 
They act by intracellular receptors to 
change transcription, that is, to change 
the DNA expression, or the gene 
expression. 
They're slow acting, and they're going to 
have long half-lives. 
Third we have binding proteins, which are 
called carriers that regulate the hormone 
availability to the target cell that 
regulate the physiologic function and the 
half lives. 
The carriers extend the half lives of 
these hormones. 
Fourth, the hormone release is under 
neural control, hormonal control, 
nutrient control or ion control. 
So, we can have different types of 
signals, which are going to regulate 
whether or not the hormone is going to be 
secreted or be synthesized and secreted. 
And five, signaling is regulated by 
changing the plasma, hormone 
concentration. 
This is, this is by far the most common 
site for regulation but you can also 
change the target cell sensitivity. 
And you can do so by removing the 
receptors from the cells surface or you 
can simply uncouple the receptors so that 
you can bind the hormone to the receptor. 
But it doesn't activate the second 
messenger signaling within the cell. 
So, it's effectively turned off. 
So, it's a desensitzed receptor. 
Okay, so we will come back and look at 
all of these different points when we are 
dealing with the endocrine systems 
themselves. 
With all the different individual 
endocrine glands, much later in the 
course. 
Got to see them 

